The long-term goal of the project is to more precisely define the roles of parathyroid hormone and calcitonin in calcium homeostasis. In line with this goal is the objective to assess the reliability of plasma immunoreactive parathyroid hormone concentration as an index of hormone secretion rate. The existence of biologically inert immunoreactive hormonal fragments in peripheral blood has raised doubt regarding the significance of the concentration of immunoreactivity in plasma. Several methods are being employed to assess the significance of plasma immunoreactive hormone concentration. These are: (1) direct measurement of secretion rate by collection and radioimmunoassay of parathyroid gland effluent blood, (2) indirect estimates of secretory rate derived from metabolic clearance rate of exogenous hormone, (3) studies of the molecular nature (i.e., intact hormone vs peptide fragments) of immunoreactive material in glandular effluent and peripheral blood, and (4) estimates of rate of disappearance of intact hormone and hormonal fragments from the circulation. From these studies we hope to determine: (1) whether changes in plasma immunoreactive hormone concentration accurately reflect changes in secretion rate, (2) whether indirect estimates of secretory rate derived from clearance data provide a reliable index of endocrine status, (3) whether some component of the plasma immunoreactivity (e.g., intact hormone) may provide a more reliable index of parathyroid activity.